Conference Day Two

Friday, August 29

For the most up-to-date agenda, please download the full event guide

7:30 am Morning Check-In: Served with Coffee & Light Breakfast

7:55 am Chair’s Opening Remarks

REFINING PRECLINICAL STRATEGY & TRANSLATIONAL CONFIDENCE FOR CNS-DIRECTED OLIGONUCLEOTIDE THERAPEUTICS

8:00 am Advancing RNA Editing Therapeutics for Rett Syndrome: Targeting the Root Cause with CNS-Directed Oligonucleotides

Synopsis

  • Introducing ProQR’s RNA editing platform and its potential to correct disease causing mutations in MECP2, the primary gene implicated in Rett Syndrome
  • Highlighting preclinical data demonstrating targeted editing in the brain using CNS-delivery conjugates and oligonucleotide-based strategies
  • Discuss the translational path, including biomarker strategies and candidate selection from non-human primate (NHP) studies, to inform clinical entry
  • Outline the near-term development timeline with clinical candidate nominations expected this year and next, and reflect on parallel efforts in liver-directed RNA editing

8:30 am Rational ASO Design in CNS Disorders: Cell-Type Targeting & Functional Validation in Complex BBBoid In Vitro Systems

  • Alice Stanton Postdoctoral Fellow, Massachusetts Institute of Technology

Synopsis

  • Design antisense oligonucleotides against genetically defined mutations in diseases like Alzheimer’s, ALS, and autism offers a powerful advantage when using in vitro models that accurately reflect the human genetic background
  • Discuss the importance of assessing the functional consequences of target modulation, leveraging multiplexed molecular and phenotypic readouts to understand downstream effects in disease-relevant pathways
  • Iterative optimization of ASO chemistry, dosing, and delivery enables enhanced cell-type specificity, which is critical when working without access to human in vivo systems
  • Develop and tailor platform technologies that can adapt to disease-specific needs is key to building biomimetic in vitro systems with translational relevance across neurodegenerative and neuropsychiatric disorders

9:00 am Harnessing a Large Animal Model to Overcome Translational Barriers in Angelman Syndrome

  • Scott V. Dindot Executive Director of Molecular Genetics, Ultragenyx Pharmaceuticals

Synopsis

  • Unpack why mouse models fail to recapitulate Angelman syndrome phenotypes and challenges associated with rodent models in preclinical development
  • Rationale and characterization of the Angelman pig model, including phenotypic fidelity, regulatory implications, and translational value
  • Target discovery in a complex genomic landscape: Exploring how integrated approaches in genetics and biology helped identify functionally relevant regions for therapeutic development for Angelman syndrome

9:30 am Morning Break & Refreshments

DERISKING OLIGONUCLEOTIDE TOX PROFILES TO ENHANCE THERAPEUTIC WINDOW & BRIDGE THE TRANSLATIONAL GAP

10:30 am Translating ASO Findings to the Clinic to Transform Outcomes in Neurodevelopmental Diseases

Synopsis

  • Unveil ASO preclinical data and NHP tox package
  • Share first in human clinical data from ASO neurodevelopmental data

11:00 am Roundtable Discussion: Demonstrating Reduced Chronic Oligonucleotide Toxicity Across Both Rodents & NHP Models

Synopsis

  • Accumulate chronic toxicity data in NHPs to understand common threads in toxicities and understand the pathology underlying chronic toxicity
  • Build cutting edge rodent models that can recapitulate chronic oligonucleotide toxicity by reverse translating observations in NHPs, overcoming the disconnect in toxicity observations between NHPs and rodent systems with oligonucleotides
  • Integrate models into clinical practice to more robustly determine candidate safety before reaching clinical trials

11:30 am Nonclinical Safety Assessment of Oligonucleotide-Based Therapeutics

  • Ron Wange Associate Director of Pharmacology & Toxicology, USA FDA (formerly)

Synopsis

  • Considerations for new chemistries and indications for oligos, as well as considerations for common, rare and ultra-rare indications
  • The FDAs views regarding platforms and platform technology
  • Evaluate what kind of safety data needs to be shown to demonstrate safety
  • Map out differences in regulatory requirements between US, Europe and more

12:00 pm Lunch & Networking Break

REFINING OLIGONUCLEOTIDE DESIGN TO ENSURE SUFFICIENT PENETRATION TO THE DEEP BRAIN TO TREAT DIVERSE DISEASES

1:00 pm Roundtable Discussion: Advancing Dose Selection & Translational PK/PD Modeling for Oligonucleotide Therapeutics & Brain Shuttles in the CNS

Synopsis

  • Leverage translational PK/PD modeling to inform dose selection and understand exposure-response relationships in the CNS for oligonucleotide-based therapies
  • Explore brain shuttle and Transferrin Receptor mediated uptake and modeling strategies to assess CNS exposure and PK ‘hit’
  • Integrate intrathecal distribution data into predictive frameworks to optimize therapeutic delivery and biodistribution
  • Case examples and lessons learned from neuroscience and oligonucleotide programs to support clinical translation and decision making

1:30 pm Leveraging Computational Modeling for Precision Intra CSF Delivery in the CNS with FalconTM

  • Kathrin Meyer Chief Scientific Officer & Head of R&D, Alcyone Therapeutics

Synopsis

  • Unpack FalconTM as a systematic approach for developing intra-CSF drugs including disease-specific understanding of CSF drug interactions, systematically optimizing drug dose, formulation and biodistribution to maximize translational success
  • Utilize high resolution MRI for better resolution and generation of computer models for advanced capacity for testing over in vivo/in vitro analysis
  • Simulate a multitude of delivery scenarios and extrapolating protocols across species, to mimic the patient condition at different disease states and reduce the reliance on extensive animal studies
  • Explore regulatory acceptance of computational modeling to support proof of concept in IND
  • Advance indications across SMA, ALS/FTD and other neurodegeneration and more

2:00 pm Afternoon Break & Refreshments

WHAT’S NEXT BEYOND TFR1 CONJUGATES? SPOTLIGHTING AN AERIAL VIEW OF AAV, SMALL MOLECULE, NANOPEPTIDE & APOE1 APPROACHES TO UNVEIL NEXT GENERATION BRAIN SHUTTLES IN NEUROLOGY

2:30 pm siRNA Brain Shuttle Strategies for Neurometabolic Modulation

  • Nicole Lykens Director of Neurobiology, Global Nucleic Acid Therapies (GNAT), Novo Nordisk

Synopsis

  • Overviewing neurometabolic axis and CS targets by targeting central regulators of hunger, satiety, and hedonic drive
  • The impact of blood-brain barrier on distribution to different brain regions as compared to intrathecal injection as illustrated through ISH imaging analysis

3:00 pm Panel Discussion: Brain Shuttles Beyond TFR1: What Will Be the Next Hot Brain Shuttle?

  • Deepak Sampath Senior Vice President, Head of Research, Ultragenyx Pharmaceuticals
  • Nicole Lykens Director of Neurobiology, Global Nucleic Acid Therapies (GNAT), Novo Nordisk

Synopsis

  • Evaluate the opportunities in overcoming target delivery challenges with TfR1 overexpression and off-target specificity
  • Explore small molecules, APOE1 peptides, nanopeptides, carbohydrates, LNPs as alternative ligands comparing pros, cons and negatives; evaluating opportunities where different ligands might be more ‘fit-for-purpose’

3:30 pm Panel Discussion: The Future of Oligonucleotide Therapeutics: Where Will the Field Be in 5 Years?

  • Paul Nioi Senior Vice President, Research, Alnylam Pharmaceuticals
  • Jimmy Weterings Vice President, Head of Oligonucleotide Therapeutics, Bonito Biosciences
  • Naim Nazef Vice President, Oligonucleotide Chemistry, Denali Therapeutics Inc.

Synopsis

  • How will advances in conjugation strategies, nanoparticle formulations, and tissue-specific targeting improve oligonucleotide biodistribution and efficacy?
  • Beyond ALS, Huntington’s Disease & Alzheimer’s. What new indications, such as neurogenetic, epilepsies, neurodevelopmental and neuropsychiatric, are emerging for oligonucleotide-based therapies?
  • What hurdles remain in scaling oligonucleotide production, and how will evolving regulatory frameworks shape the clinical and commercial landscape?
  • How will AI and ML accelerate oligonucleotide drug discovery, from sequence optimization to in silico toxicity prediction?

4:00 pm Chair’s Closing Remarks

4:05 pm End of Conference Day One